Reliable measurement of auditory-driven gamma synchrony with a single EEG electrode: A simultaneous EEG-MEG study.

OBJECTIVE: Auditory-driven gamma synchrony (GS) is linked to the function of a specific cortical circuit based on a parvalbumin+ and pyramidal neuron loop. This circuit is impaired in neuropsychiatric conditions (i.e. schizophrenia, Alzheimer's disease, stroke etc.) and its relevance in clinical practice is increasingly being recognized. Auditory stimulation at a typical gamma frequency of 40 Hz can be applied as a 'stress test' of excitation/inhibition (E/I) of the entire cerebral cortex, to drive GS and record it with magnetoencephalography (MEG) or high-density electroencephalography (EEG). However, these two techniques are costly and not widely available. Therefore, we assessed whether a single EEG electrode is sufficient to provide an accurate estimate of the auditory-driven GS level of the entire cortical surface while expecting the highest correspondence in the auditory and somatosensory cortices. METHODS: We measured simultaneous EEG-MEG in 29 healthy subjects, utilizing 3 EEG electrodes (C4, F4, O2) and a full MEG setup. Recordings were performed during binaural exposure to auditory gamma stimulation and during silence. We compared GS measurement of each of the three EEG electrodes separately against full MEG mapping. Time-resolved phase locking value (PLVt) was computed between EEG signals and cortex reconstructed MEG signals. RESULTS: During auditory stimulation, but not at rest, EEG captures a significant amount of GS, especially from both auditory cortices and motor-premotor regions. This was especially true for frontal (C4) and central electrodes (F4). DISCUSSION AND CONCLUSIONS: While hd-EEG and MEG are necessary for accurate spatial mapping of GS at rest and during auditory stimulation, a single EEG channel is sufficient to detect the global level of GS. These results have great translational potential for mapping GS in standard clinical settings.

Neurophysiological, structural, and molecular alterations in the prefrontal and auditory cortices following noise-induced hearing loss.

It is well established that hearing loss can lead to widespread plasticity within the central auditory pathway, which is thought to contribute to the pathophysiology of audiological conditions such as tinnitus and hyperacusis. Emerging evidence suggests that hearing loss can also result in plasticity within brain regions involved in higher-level cognitive functioning like the prefrontal cortex; findings which may underlie the association between hearing loss and cognitive impairment documented in epidemiological studies. Using the 40-Hz auditory steady state response to assess sound-evoked gamma oscillations, we previously showed that noise-induced hearing loss results in impaired gamma phase coherence within the prefrontal but not the auditory cortex. To determine whether region-specific structural or molecular changes accompany this differential plasticity following hearing loss, in the present study we utilized Golgi-Cox staining to assess dendritic organization and synaptic density, as well as Western blotting to measure changes in synaptic signaling proteins in these cortical regions. We show that following noise exposure, impaired gamma phase coherence within the prefrontal cortex is accompanied by alterations in pyramidal cell dendritic morphology and decreased expression of proteins involved in GABAergic (GAD65) and glutamatergic (NR2B) neurotransmission; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In contrast to the noise-induced effects we observed in the prefrontal cortex, plasticity in the auditory cortex was characterized by an increase in NR2B suggesting increased excitability, as well as increases in the synaptic proteins PSD95 and synaptophysin within the auditory cortex. Overall, our results highlight the disparate effect of noise-induced hearing loss on auditory and higher-level brain regions as well as potential structural and molecular mechanisms by which hearing loss may contribute to impaired cognitive and sensory functions mediated by the prefrontal and auditory cortices.

Estimation of Hearing Thresholds with Auditory Steady-State Responses to Narrow-Band Chirps in Children.

OBJECTIVE: The aim of this study was to evaluate the utility of auditory steady-state responses (ASSRs) to narrow-band chirps (NB-chirps) for estimating hearing levels in children. DESIGN: Thresholds from the NB-chirp ASSR were evaluated in 30 sedated children with normal hearing or hearing loss. The correlation between the NB-chirp ASSR and pure-tone audiometry (PTA) thresholds was analyzed, and the difference score (DS) between these thresholds was calculated. Data from the NB-chirp ASSR were compared to retrospective data from conventional ASSR to exponentially amplitude-modulated tones in 25 sedated children. RESULTS: Positive correlations between the NB-chirp ASSR and PTA thresholds were found at 500, 1,000, 2,000, and 4,000 Hz. Multiple comparisons of the DSs for the NB-chirp ASSR and PTA revealed significant differences at 500-2,000 Hz and 4,000 Hz, as well as 1,000-2,000 Hz, and 4,000 Hz. Comparisons of the DSs demonstrated that the DS of the NB-chirp ASSR was significantly smaller than that of the conventional ASSR at 2,000 Hz. Furthermore, the testing times for the NB-chirp ASSR were significantly shorter than those for the conventional ASSR. CONCLUSION: The NB-chirp ASSR closely reflected the PTA thresholds, and the testing time was shorter than that of the conventional ASSR. Thus, this study demonstrated that the NB-chirp ASSR is useful for hearing threshold estimation in children.

Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1 years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

Gamma auditory steady-state response as a promising electrophysiological biomarker for depression: an in vivo study with chronic unpredictable mild stress (CUS)-induced rats.

Gamma oscillations play a functional role in brain cognitions. Recently, auditory steady-state response (ASSR) has been reported abnormally in depression clinically, particularly in the low-gamma band. However, clinical electroencephalography research has challenges obtaining pure signals straight from the source level, making information isolation and precise localization difficult. Besides, the ASSR deficits pattern remains unclear. Herein, we focused on the origin of ASSR-primary auditory cortex (A1), the central node in the auditory pathway. We assessed the evoked-power and phase-synchronization using local field potentials (LFP) in depression (n = 21) and control (n = 22) rats. Subsequent processing of the received auditory information was examined using event-related potentials (AEPs). Results showed that depressed rats exhibited significant gamma ASSR impairments in peak-to-peak amplitude, inter-trial phase coherence, and signal-to-noise ratio. These deficits were more pronounced during 40-Hz auditory stimuli in right-A1, indicating severe gamma network abnormalities in the right auditory pathway. Besides, increased N2 and P3 amplitudes in depression group were found, indicating excessive inhibitory control and contextual processing. Taken together, these ASSR abnormalities have a high specificity of more than 90% and high sensitivity of more than 80% to distinguish depression under 40-Hz auditory stimuli. Our findings provided an abnormal gamma network in the auditory pathway, as a promising diagnostic biomarker in the future.

Spatiotemporal connectivity maps abnormal communication pathways in major depressive disorder underlying gamma oscillations.

Auditory steady-state response underlying gamma oscillations (gamma-ASSR) have been explored in patients with major depressive disorder (MDD), while ignoring the spatiotemporal dynamic characteristics. This study aims to construct dynamic directed brain networks to explore the disruption of spatiotemporal dynamics underlying gamma-ASSR in MDD. This study recruited 29 MDD patients and 30 healthy controls for a 40 Hz auditory steady-state evoked experiment. The propagation of gamma-ASSR was divided into early, middle, and late time interval. Partial directed coherence was applied to construct dynamic directed brain networks based on graph theory. The results showed that MDD patients had lower global efficiency and out-strength in temporal, parietal, and occipital regions over three time intervals. Additionally, distinct disrupted connectivity patterns occurred in different time intervals with abnormalities in the early and middle gamma-ASSR in left parietal regions cascading forward to produce dysfunction of frontal brain regions necessary to support gamma oscillations. Furthermore, the early and middle local efficiency of frontal regions were negatively correlated with symptom severity. These findings highlight patterns of hypofunction in the generation and maintenance of gamma-band oscillations across parietal-to-frontal regions in MDD patients, which provides novel insights into the neuropathological mechanism underlying gamma oscillations associated with aberrant brain network dynamics of MDD.

Individualized EEG-Based Neurofeedback Targeting Auditory Steady-State Responses: A Proof-of-Concept Study.

Gamma-band (> 30 Hz) brain oscillatory activity is linked with sensory and cognitive processes and exhibits abnormalities in neuropsychiatric disorders. Therefore, neuromodulation techniques targeting gamma activity are being developed. One promising approach is neurofeedback (NFB) which is based on the alteration of brain responses via online feedback. However, the existing gamma-based NFB systems lack individualized approach. In the present work, we developed and tested an individualized EEG-NFB system. 46 healthy volunteers participated in three sessions on separate days. Before NFB training, individual gamma frequency (IGF) was estimated using chirp-modulated auditory stimulation (30-60 Hz). Participants were subjected to IGF-increase (if IGF was ≤ 45 Hz) or IGF-decrease conditions (if IGF was > 45 Hz). Gamma-band responses were targeted during NFB training, in which participants received auditory steady-state stimulation at frequency slightly above or below IGF and were instructed to try to increase their response while receiving real-time visual feedback. Each time a pre-defined response goal was reached, stimulation frequency was either increased or decreased. After training, IGF was reassessed. Experimental group participants were divided into equal groups based on the median success rate during NFB training. The results showed that high-responders had a significantly higher IGF modulation compared to control group, while low-responders did not differ from controls. No differences in IGF modulation were found between sessions and between NFB repetitions in all participant groups. The initial evaluation of the proposed EEG-NFB system showed potential to modulate IGF. Future studies could investigate longer-lasting electrophysiological and behavioural effects of the application of ASSR/IGF-based NFB system in clinical populations.

Pulsatile modulation greatly enhances neural synchronization at syllable rate in children.

Neural processing of the speech envelope is of crucial importance for speech perception and comprehension. This envelope processing is often investigated by measuring neural synchronization to sinusoidal amplitude-modulated stimuli at different modulation frequencies. However, it has been argued that these stimuli lack ecological validity. Pulsatile amplitude-modulated stimuli, on the other hand, are suggested to be more ecologically valid and efficient, and have increased potential to uncover the neural mechanisms behind some developmental disorders such a dyslexia. Nonetheless, pulsatile stimuli have not yet been investigated in pre-reading and beginning reading children, which is a crucial age for developmental reading research. We performed a longitudinal study to examine the potential of pulsatile stimuli in this age range. Fifty-two typically reading children were tested at three time points from the middle of their last year of kindergarten (5 years old) to the end of first grade (7 years old). Using electroencephalography, we measured neural synchronization to syllable rate and phoneme rate sinusoidal and pulsatile amplitude-modulated stimuli. Our results revealed that the pulsatile stimuli significantly enhance neural synchronization at syllable rate, compared to the sinusoidal stimuli. Additionally, the pulsatile stimuli at syllable rate elicited a different hemispheric specialization, more closely resembling natural speech envelope tracking. We postulate that using the pulsatile stimuli greatly increases EEG data acquisition efficiency compared to the common sinusoidal amplitude-modulated stimuli in research in younger children and in developmental reading research.

Neural synchronization and intervention in pre-readers who later on develop dyslexia.

A growing number of studies has investigated temporal processing deficits in dyslexia. These studies largely focus on neural synchronization to speech. However, the importance of rise times for neural synchronization is often overlooked. Furthermore, targeted interventions, phonics-based and auditory, are being developed, but little is known about their impact. The current study investigated the impact of a 12-week tablet-based intervention. Children at risk for dyslexia received phonics-based training, either with (n = 31) or without (n = 31) auditory training, or engaged in active control training (n = 29). Additionally, neural synchronization and processing of rise times was longitudinally investigated in children with dyslexia (n = 26) and typical readers (n = 52) from pre-reading (5 years) to beginning reading age (7 years). The three time points in the longitudinal study correspond to intervention pre-test, post-test and consolidation, approximately 1 year after completing the intervention. At each time point neural synchronization was measured to sinusoidal stimuli and pulsatile stimuli with shortened rise times at syllable (4 Hz) and phoneme rates (20 Hz). Our results revealed no impact on neural synchronization at syllable and phoneme rate of the phonics-based and auditory training. However, we did reveal atypical hemispheric specialization at both syllable and phoneme rates in children with dyslexia. This was detected even before the onset of reading acquisition, pointing towards a possible causal rather than consequential mechanism in dyslexia. This study contributes to our understanding of the temporal processing deficits underlying the development of dyslexia, but also shows that the development of targeted interventions is still a work in progress.

Suppression of Low-Frequency Gamma Oscillations by Activation of 40-Hz Oscillation.

Gamma oscillations have received considerable attention owing to their association with cognitive function and various neuropsychiatric disorders. However, interactions of gamma oscillations at different frequency bands in humans remain unclear. In the present magnetoencephalographic study, brain oscillations in a wide frequency range were examined using a time-frequency analysis during the 20-, 30-, 40-, and 50-Hz auditory stimuli in 21 healthy subjects. First, dipoles for auditory steady-state response (ASSR) were estimated and interaction among oscillations at 10-60 Hz was examined using the source strength waveforms. Results showed the suppression of ongoing low-gamma oscillations at approximately 30 Hz during stimulation at 40 Hz. Second, multi-dipole analyses suggested that the main dipole for ASSR and dipoles for suppressed low-frequency gamma oscillations were distinct. Third, an all-sensor analysis was performed to clarify the distribution of the 40-Hz ASSR and suppression of low-frequency gamma oscillations. Notably, the area of suppression surrounded the center of the 40-Hz ASSR and showed a trend of extending to the vertex, indicating that different groups of neurons were responsible for these two gamma oscillations and that the 40-Hz oscillation circuit have specific inhibitory innervation to the low-gamma circuit.

Extraction of Individual EEG Gamma Frequencies from the Responses to Click-Based Chirp-Modulated Sounds.

Activity in the gamma range is related to many sensory and cognitive processes that are impaired in neuropsychiatric conditions. Therefore, individualized measures of gamma-band activity are considered to be potential markers that reflect the state of networks within the brain. Relatively little has been studied in respect of the individual gamma frequency (IGF) parameter. The methodology for determining the IGF is not well established. In the present work, we tested the extraction of IGFs from electroencephalogram (EEG) data in two datasets where subjects received auditory stimulation consisting of clicks with varying inter-click periods, covering a 30-60 Hz range: in 80 young subjects EEG was recorded with 64 gel-based electrodes; in 33 young subjects, EEG was recorded using three active dry electrodes. IGFs were extracted from either fifteen or three electrodes in frontocentral regions by estimating the individual-specific frequency that most consistently exhibited high phase locking during the stimulation. The method showed overall high reliability of extracted IGFs for all extraction approaches; however, averaging over channels resulted in somewhat higher reliability scores. This work demonstrates that the estimation of individual gamma frequency is possible using a limited number of both the gel and dry electrodes from responses to click-based chirp-modulated sounds.

Reliability and Accuracy of Chirp Based Multiple Auditory Steady State Response (MSSR) and Auditory Brainstem Response (ABR) in Children.

OBJECTIVE: The purpose of this study was to compare the reliability and accuracy of chirp-based Multiple Auditory Steady State Response (MSSR) and Auditory Brainstem Response (ABR) in children. METHODS: The prospective clinical study was conducted at Selayang Hospital (SH) and Hospital Canselor Tuanku Muhriz (HCTM) within one year. A total of 38 children ranging from 3 to 18 years old underwent hearing evaluation using ABR tests and MSSR under sedation. The duration of both tests were then compared. RESULTS: The estimated hearing threshold of frequency specific chirp MSSR showed good correlation with ABR especially in higher frequencies such as 2000 Hz and 4000Hz with the value of cronbach alpha of 0.890, 0.933, 0.970 and 0.969 on 500Hz, 1000Hz, 2000Hz and 4000Hz. The sensitivity of MSSR is 0.786, 0.75, 0.957 and 0.889 and specificity is 0.85, 0.882, 0.979 and 0.966 over 500Hz, 1000Hz, 2000Hz and 4000Hz. The duration of MSSR tests were shorter than ABR tests in normal hearing children with an average of 35.3 minutes for MSSR tests and 46.4 minutes for ABR tests. This can also be seen in children with hearing loss where the average duration for MSSR tests is 40.0 minutes and 52.0 minutes for ABR tests. CONCLUSION: MSSR showed good correlation and reliability in comparison with ABR especially on higher frequencies. Hence, MSSR is a good clinical test to diagnose children with hearing loss.

Auditory driven gamma synchrony is associated with cortical thickness in widespread cortical areas.

OBJECTIVE: Gamma synchrony is a fundamental functional property of the cerebral cortex, impaired in multiple neuropsychiatric conditions (i.e. schizophrenia, Alzheimer's disease, stroke etc.). Auditory stimulation in the gamma range allows to drive gamma synchrony of the entire cortical mantle and to estimate the efficiency of the mechanisms sustaining it. As gamma synchrony depends strongly on the interplay between parvalbumin-positive interneurons and pyramidal neurons, we hypothesize an association between cortical thickness and gamma synchrony. To test this hypothesis, we employed a combined magnetoencephalography (MEG) - Magnetic Resonance Imaging (MRI) study. METHODS: Cortical thickness was estimated from anatomical MRI scans. MEG measurements related to exposure of 40 Hz amplitude modulated tones were projected onto the cortical surface. Two measures of cortical synchrony were considered: (a) inter-trial phase consistency at 40 Hz, providing a vertex-wise estimation of gamma synchronization, and (b) phase-locking values between primary auditory cortices and whole cortical mantle, providing a measure of long-range cortical synchrony. A correlation between cortical thickness and synchronization measures was then calculated for 72 MRI-MEG scans. RESULTS: Both inter-trial phase consistency and phase locking values showed a significant positive correlation with cortical thickness. For inter-trial phase consistency, clusters of strong associations were found in the temporal and frontal lobes, especially in the bilateral auditory and pre-motor cortices. Higher phase-locking values corresponded to higher cortical thickness in the frontal, temporal, occipital and parietal lobes. DISCUSSION AND CONCLUSIONS: In healthy subjects, a thicker cortex corresponds to higher gamma synchrony and connectivity in the primary auditory cortex and beyond, likely reflecting underlying cell density involved in gamma circuitries. This result hints towards an involvement of gamma synchrony together with underlying brain structure in brain areas for higher order cognitive functions. This study contributes to the understanding of inherent cortical functional and structural brain properties, which might in turn constitute the basis for the definition of useful biomarkers in patients showing aberrant gamma synchronization.

Effect of dopamine receptor-related compounds on naïve common marmosets for auditory steady-state response.

Abnormalities of auditory steady-state responses (ASSRs) and the effects of antipsychotic drugs on ASSRs have been investigated in patients with schizophrenia. It is presumed that drugs do not directly affect ASSRs because its abnormalities are associated with schizophrenia. Therefore, to investigate the direct effect of drugs on ASSRs, we established an ASSR evaluation system for common marmosets in a naïve state. Dopamine D1 receptor stimulation (SKF-81297, 2 mg/kg ip) significantly increased evoked power (EP) at 40 Hz. The phase locking factor (PLF) was increased significantly at 20, 30, 40, and 80 Hz. However, administration of a dopamine D1 receptor antagonist (SCH-39166, 0.3 mg/kg ip) resulted in a significant decrease in EP and PLF at 30 Hz. Dopamine D2 receptor stimulation (quinpirole, 1 mg/kg im) tended to increase EP and induced power (IP) at all frequencies, and a significant difference was observed at 30 Hz IP. There was no change in PLF at all frequencies. In addition, dopamine D2 receptor blockade (raclopride, 3 mg/kg ip) reduced EP and PLF at 30 Hz. Subcutaneous administration of the serotonin dopamine antagonist, risperidone (0.3 mg/kg), tended to increase IP and decrease PLF, but not significantly. Taken together, it is possible to compare the differences in the mode of action of drugs on ASSRs using naïve nonhuman primates.NEW & NOTEWORTHY We measured the effects of dopamine receptor-related compounds on ASSR in marmosets. D1 receptor stimulation increased the phase locking factor (PLF) and evoked power (EP), and reduced the induced power (IP). D2 receptor stimulation increased the IP. D1 and D2 receptor blockers reduced the PLF and EP at 30 Hz. Different modes of action of various drugs related to psychiatric disorders were evaluated by administering antipsychotic drugs to naïve marmosets.

The age-related changes in 40 Hz Auditory Steady-State Response and sustained Event-Related Fields to the same amplitude-modulated tones in typically developing children: A magnetoencephalography study.

Recent studies have revealed that gamma-band oscillatory and transient evoked potentials may change with age during childhood. It is hypothesized that these changes can be associated with a maturation of GABAergic neurotransmission and, subsequently, the age-related changes of excitation-inhibition balance in the neural circuits. One of the reliable paradigms for investigating these effects in the auditory cortex is 40 Hz Auditory Steady-State Response (ASSR), where participants are presented with the periodic auditory stimuli. It is known that such stimuli evoke two types of responses in magnetoencephalography (MEG)-40 Hz steady-state gamma response (or 40 Hz ASSR) and auditory evoked response called sustained Event-Related Field (ERF). Although several studies have been conducted in children, focusing on the changes of 40 Hz ASSR with age, almost nothing is known about the age-related changes of the sustained ERF to the same periodic stimuli and their relationships with changes in the gamma strength. Using MEG, we investigated the association between 40 Hz steady-state gamma response and sustained ERF response to the same stimuli and also their age-related changes in the group of 30 typically developing 7-to-12-year-old children. The results revealed a tight relationship between 40 Hz ASSR and ERF, indicating that the age-related increase in strength of 40 Hz ASSR was associated with the age-related decrease of the amplitude of ERF. These effects were discussed in the light of the maturation of the GABAergic system and excitation-inhibition balance development, which may contribute to the changes in ASSR and ERF.

Auditory steady state responses elicited by silent gaps embedded within a broadband noise.

BACKGROUND: Auditory temporal processing plays an important role in speech comprehension. Usually, behavioral tests that require subjects to detect silent gaps embedded within a continuous sound are used to assess the ability of auditory temporal processing in humans. To evaluate auditory temporal processing objectively, the present study aimed to measure the auditory steady state responses (ASSRs) elicited by silent gaps of different lengths embedded within a broadband noise. We presented a broadband noise with 40-Hz silent gaps of 3.125, 6.25, and 12.5 ms. RESULTS: The 40-Hz silent gaps of 3.125, 6.25, and 12.5 ms elicited clear ASSRs. Longer silent gaps elicited larger ASSR amplitudes and ASSR phases significantly differed between conditions. CONCLUSION: The 40 Hz gap-evoked ASSR contributes to our understanding of the neural mechanisms underlying auditory temporal processing and may lead to the development of objective measures of auditory temporal acuity in humans.

Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans.

Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.

Neuronal imbalance of excitation and inhibition in schizophrenia: a scoping review of gamma-band ASSR findings.

Recent empirical findings suggest that altered neural synchronization, which is hypothesized to be associated with an imbalance of excitatory (E) and inhibitory (I) neuronal activities, may underlie a core pathophysiological mechanism in patients with schizophrenia. The auditory steady-state response (ASSR) examined by electroencephalography (EEG) and magnetoencephalography (MEG) has been proposed as a potential biomarker for evaluating altered neural synchronization in schizophrenia. For this review, we performed a comprehensive literature search for papers published between 1999 and 2021 examining ASSRs in patients with schizophrenia. Almost all EEG-ASSR studies reported gamma-band ASSR reductions, especially to 40-Hz stimuli both in power and/or phase synchronization in chronic and first-episode schizophrenia. In addition, similar to EEG-ASSR findings, MEG-ASSR deficits to 80-Hz stimuli (high gamma) have been reported in patients with schizophrenia. Moreover, the 40-Hz ASSR is likely to be a predictor of the onset of schizophrenia. Notably, increased spontaneous (or ongoing) broadband (30-100 Hz) gamma power has been reported during ASSR tasks, which resembles the increased spontaneous gamma activity reported in animal models of E/I imbalance. Further research on ASSRs and evoked and spontaneous gamma oscillations is expected to elucidate the pathophysiology of schizophrenia with translational implications.

Automatic audiometry using auditory steady-state response and sequential test strategy applied to volunteers with normal hearing.

PURPOSE: In the present study, a new procedure to perform automatic audiometry using multifrequency Auditory Steady-State Response (ASSR) is proposed. METHODS: The automatic audiometry procedure consists of detecting the presence of multifrequency ASSR in real-time using the sequential test strategy and by adjusting the stimulus intensity independently. The ASSR audiometric thresholds of 18 adult volunteers with normal hearing were determined by automatically (four simultaneous frequencies per ear) at modulation frequencies in the 80 Hz range. The exam time and the difference between ASSR thresholds and pure-tone behavioural hearing thresholds were estimated as performance measures. RESULTS: The results showed that automatic audiometry can reduce the number of intensity levels used to obtain the ASSR threshold by up to 58% when compared to audiometry without using the techniques applied in automatic audiometry. In addition, the average of the difference between ASSR thresholds and Pure-Tone Behavioural Hearing thresholds was around 19 dB, which is similar to the results reported in similar studies. CONCLUSIONS: The audiometric procedure proposed in this study is fully automatic, i.e., does not require any human supervision throughout the exam, and is able to significantly reduce the conventional exam time.

Assessing Agreement between Frequency-Specific Chirp Auditory Steady-State Response and Pure Tone Audiometry in Adults by Intraclass Correlation Coefficient.

INTRODUCTION: Chirp auditory steady-state response (ASSR) can be used to assess frequency-specific hearing thresholds. However, its reliability has not been confirmed yet. The purpose of this proposed study is to analyze the agreement of thresholds measured by chirp-ASSR and pure tone audiometry (PTA) to investigate the value of chirp-ASSR in hearing threshold evaluation. METHODS: Participants with normal hearing (age: 18-66, 108 ears) and patients with sensorineural hearing loss (age: 22-82, 75 ears) were tested using PTA and chirp-ASSR at 0.5, 1, 2, and 4 kHz, respectively. Intraclass correlation coefficient (ICC) and Bland-Altman plot were introduced to analyze the agreement between the 2 methods. RESULTS: One-hundred eight participants underwent both chirp-ASSR and PTA to estimate their thresholds. The ICCs yielded by these 2 methods are 0.757, 0.893, 0.883, and 0.921 (p < 0.001) at 0.5, 1, 2, and 4 kHz carrier frequency, respectively. However, there is a significant difference between the 2 methods at 2 kHz: the mean value of the ASSR thresholds is 5.27 dB HL higher than the value of PTA thresholds. Additionally, the 95% limits of agreement range from -27.48 to 26.66 dB HL at 0.5 kHz, from -18.19 to 17.87 dB HL at 1 kHz, from -12.01 to 22.55 dB HL at 2 kHz, and from -21.29 to 19.17 dB HL at 4 kHz, which are large enough to affect clinical decision-making. CONCLUSION: In this study, we have confirmed good to excellent correlation between chirp-ASSR and PTA in threshold estimation for adults with and without hearing loss. The degree of correlations is higher for participants with hearing loss and for measurements at high frequencies. However, significant systematic difference and large limits of agreement between the 2 methods have been found. These findings show that chirp-ASSR can be treated as a supplementary method to PTA when evaluating the hearing level, but the 2 methods are not interchangeable due to their systematic difference and large limits of agreement.